Spinal Cord Injury Research Research Articles

Fish Species Spinal Cord Injury Models Utility for Research: A Systematic Review of Methodologies and Outcomes

Context: Spinal cord injury (SCI) is a devastating condition that results in severe disability and significant comorbidities. The complex pathophysiology of SCI repair and difficulties understanding neural regeneration are treatment challenges. Objectives: The aim of this study is to systematically review the diverse applications of various fish species as models for SCI research. Evidence Acquisition: PRISMA guidelines were used to review observational and interventional studies that utilized fish species as SCI models, published from inception to July 2023. Two independent reviewers screened and performed the data extraction. One independent reviewer assessed the risk of bias for the included studies. Results: Five thousand six hundred and thirty-three records were reviewed, and 144 met the inclusion criteria and were categorized by fish species. The majority of studies employed complete transection injuries, with the remainder being crush injuries, laser injuries, electro-ablations, and demyelination with substances. Zebrafish (Danio rerio) were most commonly utilized 102/144 (71%), primarily with larval models. Other models included Lamprey (Petromyzon marinus and Lethenteron reissneri); Goldfish (Carassius auratus); European eel (Anguilla Anguilla); Knifefish (Apteronotus leptorhynchus and Apteronotus albifrons); Sailfin Molly (Poecilia latipinna); and African turquoise killifish (Nothobranchius furzeri). Conclusions: This systematic review highlights that fish models, particularly zebrafish, goldfish, and European eels, are important models for further defining SCI pathophysiology and regenerative processes. These models provide a less complex model to gain insights into apoptosis and glial networks.

The correlation of neurosurgery motor examinations with ISNCSCI motor examinations in patients with spinal cord injury: a multicenter TRACK-SCI study.

The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) assessment is the gold standard for evaluation of neurological function after spinal cord injury (SCI). Although it is an invaluable tool for diagnostic and research purposes, it is time consuming and can be impractical in acute injury settings. Clinical neurosurgery motor examinations (NMEs) could serve as an expeditious surrogate for SCI research when ISNCSCI motor examinations are not feasible. The aim of this study was to evaluate the agreement between motor examinations performed by the neurosurgery clinical team and ISNCSCI examiners. The multicenter prospective Transforming Research and Clinical Knowledge in Spinal Cord Injury (TRACK-SCI) registry was queried to identify patients with recorded neurosurgery and research motor examinations within 24 hours of each other. Pearson correlations and modified Bland-Altman analyses were performed using data from matching upper-extremity, lower-extremity, and combined examinations. Kappa analysis was used to test interrater reliability with respect to determination of American Spinal Injury Association Impairment Scale (AIS) grade. There were 72 pairs of matching clinical and research examinations in 63 patients. NME scores were strongly correlated with ISNCSCI motor scores (R = 0.962, p < 0.001). Both upper- and lower-extremity NME scores were strongly correlated with upper- and lower-extremity ISNCSCI motor scores, respectively (R = 0.939, p < 0.001; and R = 0.959, p < 0.001, respectively). In modified Bland-Altman analyses, total, upper-extremity, and lower-extremity NME scores and ISNCSCI motor scores showed low systematic bias and high agreeability (total: bias = 0.3, limit of agreement [LoA] = 36.6; upper extremity: bias = -0.5, LoA = 17.6; lower extremity: bias = 0.8, LoA = 24.0). There were 66 pairs of examinations that had thorough sensory and rectal examinations for AIS grade calculation. Using kappa analysis to test the interrater reliability of AIS grade calculation using NME versus ISNCSCI motor scores, the authors found a weighted kappa of 0.883 (SE 0.061, 95% CI 0.736-0.976), indicating strong agreement. Overall, this study suggests that ISNCSCI motor scores and NME scores are strongly correlated and highly agreeable. When conducting SCI research, a thorough clinical motor examination may be a useful surrogate when ISNCSCI examinations are missing.

Combining clinically common drugs with hindlimb stretching in spinal cord injured rodents.

Preclinical pilot study. To explore peripheral and central nociceptive mechanisms that contribute to muscle stretch-induced locomotor deficits following spinal cord injury. Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA. Ten female Sprague-Dawley rats received moderate, 25 g/cm T10 contusion injuries and recovered for 4 weeks. Rats were divided into three groups: Morphine/Ibuprofen-treated, Acetaminophen/Baclofen-treated, and saline control. Each group received daily hindlimb muscle stretching during weeks 4, 5, 9, and 10 post-injury and drugs were administered with stretching during weeks 4 and 9 only. Locomotor function was assessed throughout the experiment using the BBB Open Field Locomotor Scale. Hindlimb responses including spasticity, writhing, and clonic-like vibrations during muscle stretching were classified and scored. Consistent with our previous studies, hindlimb muscle stretching caused significant deficits in locomotor recovery following spinal cord injury. Baclofen and Ibuprofen partially mitigated the stretching effect, but none of the drugs significantly prevented the drop in locomotor function during stretching. Interestingly, treatment with Baclofen or Ibuprofen significantly reduced hindlimb responses such as spasticity and writhing during stretching, while Morphine exacerbated clonic-like vibrations in response to stretching maneuvers. These findings suggest that stretching may inhibit locomotor recovery through combined mechanisms of peripheral inflammation and sensitization of nociceptive afferents. When combined with central sprouting and loss of descending controls after SCI, this results in exaggerated nociceptive input during stretching. The inability of the applied clinical drugs to mitigate the detrimental effects of stretching highlights the complexity of the stretching phenomenon and emphasizes the need for further investigation.

A novel minimally invasive and versatile kyphoplasty balloon-based model of porcine spinal cord injury.

Spinal cord injury (SCI) animal models often utilize an open surgical laminectomy, which results in animal morbidity and also leads to changes in spinal canal diameter, spinal cord perfusion, cerebrospinal fluid flow dynamics, and spinal stability which may confound SCI research. Moreover, the use of open surgical laminectomy for injury creation lacks realism when considering human SCI scenarios. We developed a novel, image-guided, minimally invasive, large animal model of SCI which utilizes a kyphoplasty balloon inserted into the epidural space via an interlaminar approach without the need for open surgery. The model was validated in 5 Yucatán pigs with imaging, neurofunctional, histologic, and electrophysiologic findings consistent with a mild compression injury. Few large animal models exist that have the potential to reproduce the mechanisms of spinal cord injury (SCI) commonly seen in humans, which in turn limits the relevance and applicability of SCI translational research. SCI research relies heavily on animal models, which typically involve an open surgical, dorsal laminectomy which is inherently invasive and may have untoward consequences on animal morbidity and spinal physiology that limit translational impact. We developed a minimally invasive, large animal model of spinal cord injury which utilizes a kyphoplasty balloon inserted percutaneously into the spinal epidural space. Balloon inflation results in a targeted, compressive spinal cord injury with histological and electrophysiological features directly relevant to human spinal cord injury cases without the need for invasive surgery. Balloon inflation pressure, length of time that balloon remains inflated, and speed of inflation may be modified to achieve variations in injury severity and subtype.

The Development of Principles for Patient and Public Involvement (PPI) in Preclinical Spinal Cord Research: A Modified Delphi Study.

There is currently limited guidance for researchers on Patient and Public Involvement (PPI) for preclinical spinal cord research, leading to uncertainty about design and implementation. This study aimed to develop evidence-informed principles to support preclinical spinal cord researchers to incorporate PPI into their research. This study used a modified Delphi method with the aim of establishing consensus on a set of principles for PPI in spinal cord research. Thirty-eight stakeholders including researchers, clinicians and people living with spinal cord injury took part in the expert panel. Participants were asked to rate their agreement with a series of statements relating to PPI in preclinical spinal cord research over two rounds. As part of Round 2, they were also asked to rate statements as essential or desirable. Thirty-eight statements were included in Round 1, after which five statements were amended and two additional statements were added. After Round 2, consensus (> 75% agreement) was reached for a total of 27 principles, with 13 rated as essential and 14 rated as desirable. The principles with highest agreement related to diversity in representation among PPI contributors, clarity of the purpose of PPI and effective communication. This research developed a previously unavailable set of evidence-informed principles to inform PPI in preclinical spinal cord research. These principles provide guidance for researchers seeking to conduct PPI in preclinical spinal cord research and may also inform PPI in other preclinical disciplines. This study was conducted as part of a project aiming to develop PPI in preclinical spinal cord injury research associated with an ongoing research collaboration funded by the Irish Rugby Football Union Charitable Trust (IRFU CT) and the Science Foundation Ireland Centre for Advanced Materials and BioEngineering Research (SFI AMBER), with research conducted by the Tissue Engineering Research Group (TERG) at the RCSI University of Medicine and Health Sciences. The project aims to develop an advanced biomaterials platform for spinal cord repair and includes a PPI Advisory Panel comprising researchers, clinicians and seriously injured rugby players to oversee the work of the project. PPI is included in this study through the involvement of members of the PPI Advisory Panel in the conceptualisation of this research, review of findings, identification of key points for discussion and preparation of the study manuscript as co-authors.

Magnetic Stimulation of Gigantocellular Reticular Nucleus with Iron Oxide Nanoparticles Combined Treadmill Training Enhanced Locomotor Recovery by Reorganizing Cortico-Reticulo-Spinal Circuit.

Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms. Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs' projections and evaluate neurotransmitters' expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn. (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters' expression in anterior horn of lumbar spinal cord. These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters' expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit.

Study on spinal cord injury based on bibliometric analysis

Objectives: This article was designed to deeply analyze the research status and frontier trend of spinal cord injury (SCI), so as to accurately understand the development stage and characteristics of SCI research. Methods: By entering keywords to download literature, and applying bibliometric analysis software, and website, we find and analyze articles related to SCI from 1906 to 2024 on Web of Science, then deciphering the annual trends, countries or regions, institutions, and authors in SCI field. Results: The study found that the United States is the most productive country, which started its researches early and published articles far beyond other countries. The most powerful institution is University of Kentucky. The Journal of Research is in the leading place from journal analysis. Whereas, in terms of journal, Liu, J. is the most productive author who published 58 papers. Conclusions: Therefore, in the field of SCI, other countries need to make efforts to keep up with the United States, and try to innovate and broaden the scope of their studies. This article systematically reviews the trend and hotspot of SCI-related studies, therefore offering valuable insights for future studies.

Research hotspots and trends of microRNAs in spinal cord injury: a comprehensive bibliometric analysis.

Spinal cord injury (SCI) is a nervous system disease leading to motor and sensory dysfunction below the injury level, and can result in paralysis. MicroRNAs (miRNAs) play a key role in SCI treatment, and related research provides insights for SCI diagnosis and treatment. Bibliometrics is an important tool for literature statistics and evaluation, objectively summarizing multidimensional information. This study comprehensively overviews the field through bibliometric analysis of miRNA and SCI research, providing contemporary resources for future collaboration and clinical treatment. In this study, we searched the Web of Science Core Collection (WOSCC) database. After careful screening and data import, we extracted annual publications, citation counts, countries, institutions, authors, journals, highly cited articles, co-cited articles, keywords, and H-index. Bibliometrics and visualization analyses employed VOSviewer, CiteSpace, the R package "bibliometrix," and online analytic platforms. Using Arrowsmith, we determined miRNA-SCI relationships and discussed potential miRNA mechanisms in SCI. From 2008 to 2024, the number of related papers increased annually, reaching 754. The number of yearly publications remained high and entered a period of rapid development. Researchers from 50 countries/regions, 802 institutions, 278 journals, and 3,867 authors participated in the field. Currently, China has advantages in the number of national papers, citations, institutions, and authors. However, it is necessary to strengthen cooperation among different authors, institutions, and countries to promote the production of important academic achievements. The research in the field currently focuses on nerve injury, apoptosis, and gene expression. Future research directions mainly involve molecular mechanisms, clinical trials, exosomes, and inflammatory reactions. Overall, this study comprehensively analyzes the research status and frontier of miRNAs in SCI. A systematic summary provides a complete and intuitive understanding of the relationship between SCI and miRNAs. The presented findings establish a basis for future research and clinical application in this field.

Different subsets of V2a propriospinal neurons respond differently to spinal cord injury

While propriospinal neurons play a crucial role in recovering function post-spinal cord injury, it remains unclear whether these neurons exhibit largely similar responses to injury or if their diversity requires distinct alterations in gene expression. Here, we focused on one population of spinal neurons, the V2a class, previously shown to be important for recovery of locomotor and respiratory function after spinal cord injury. Using single nuclei gene expression analyses, we delineate substantial molecular and cellular heterogeneity of V2a propriospinal neurons subtypes in adult mice and examine how individual subtypes are altered by injury. Remarkably, a subset of V2a neurons expressing Rbms3+/Nav3+ and enriched for synaptic transmission and axon guidance molecules were found to be nearly absent following injury. The remaining V2a populations exhibited distinctive transcriptional alterations, indicating a potential rewiring of cellular interactions within the spinal cord microenvironment. Thus, our study reveals the diverse responses of propriospinal neurons to injury. These analyses provide a foundation for understanding changes in propriospinal neurons that may lead to adaptive (or maladaptive) changes in circuit function following injury. NIH R01 NS112255 (PI:Crone) Spinal Circuitry for Ventilatory Control and Compensation Craig H. Neilsen Foundation- Spinal Cord Injury Research on the Translational Spectrum (PI: Crone) Targeting propriospinal neurons to improve breathing following injury. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Breastfeeding Following Spinal Cord Injury: Consumer Guide for Mothers.

The World Health Organization (WHO) recommends that infants be breastfed exclusively for the first 6 months of age. However, there are few resources available on the effects a spinal cord injury (SCI) can have for breastfeeding mothers. It is difficult to find information to address the unique challenges women with SCI experience when planning or trying to breastfeed. Our international team, including women with SCI, health care providers, and SCI researchers, aims to address the information gap through the creation of this consumer guide. The purpose of this consumer guide is to share the most common issues women with SCI experience during breastfeeding and provide information, practical suggestions, recommendations, and key resources in lay language. General information about breastfeeding is available on the internet, in books, or from friends and health care providers. We do not intend to repeat nor replace general breastfeeding information or medical advice. Breastfeeding for mothers with SCI is complex and requires a team of health care providers with complementary expertise. Such a team may include family physician, obstetrician, physiatrist, neurologist, occupational and physical therapist, lactation consultant, midwife, and psychologist. We hope this consumer guide can serve as a quick reference guide for mothers with SCI planning of trying to breastfeed. This guide will also be helpful to health care providers as an educational tool.

The opioid buprenorphine differentially affects laryngeal and tracheal sensory receptors

The current study aims to determine mechanisms of impaired airway protection following opioid administration. Experiments were performed on N=10 anesthetized male Sprague Dawley rats. Bipolar fine wire electromyogram (EMG) wires were implanted in various muscles to evaluate breathing and swallowing. Swallows were evoked by activation of laryngeal touch receptors, tracheal mechanoreceptors, and tracheobronchial c-fibers as follows: A) Light laryngeal touch with a Von Frey filament; B) Rapid inflation of a balloon in the proximal trachea; C) Stimulation of the carina with thin polyethylene tubing. Trials were performed before and after buprenorphine administration (0.01 mg/kg IV). 2-Way ANOVA detected an effect of drug [F(1,16)=40.6, p&lt;0.0001] and stimulus [F(2,19)=4.2, p=0.03] on swallow frequency. Post hoc comparisons showed that after buprenorphine administration, laryngeal touch evoked significantly more swallows (10±4) than tracheal distension (1±1, p=0.03) or carina stimulation (1±3, p=0.04), suggesting that laryngeal sensation is critical for airway protection following opioid administration. This has implications for prevention of aspiration pneumonia in populations that have an increased risk of reduced laryngeal sensation and are commonly treated with opioids (e.g., post-surgical, critically ill, and/or head and neck cancer patients). Research reported in this abstract was supported by NIH grants NS110169, HL155721, HL163008, HD110951, NS097781, OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, and the Commonwealth of Kentucky Challenge for Excellence. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Longitudinal Assessment of Outcome Measures of Diaphragm Motor Unit Connectivity As Biomarkers of Phrenic Motor Unit Degeneration and Compensation

Phrenic motor neurons (MNs) form the final link from the central nervous system (CNS) to the diaphragm muscle. Ventilatory function is modulated by the CNS via groups of muscle fibers each controlled by a single MN (motor units). Processes such as injury, aging, and neurodegeneration can result in losses of MNs, and their motor unit (MU) counterparts, but MNs and MUs have some capacity for compensation through mechanisms such as axonal sprouting and collateral sprouting to regain connectivity with denervated muscle. Motor unit number (motor unit number estimation, MUNE), MU size (single motor unit potential amplitude, SMUP), and summated muscle excitation (compound muscle action potential amplitude, CMAP) have been used clinically and preclinically for decades to track MU connectivity but efforts have largely focused on limb muscles. We aimed to apply these measures to a model of phrenic MN degeneration (intrapleural injection of cholera toxin B fragment conjugated to saporin, CTB-SAP).We hypothesized that CTB-SAP-induced phrenic motor neuron death would result in loss of diaphragm MU number and compensatory increases in MU size. Under isoflurane anesthesia, rats were bilaterally, intrapleurally injected with CTB-SAP (25 μg) to target phrenic MNs and extra CTB (25 μg) to label surviving phrenic MNs, and control rats received unconjugated CTB (25 μg) and SAP (25 μg). Diaphragm CMAP, SMUP, and MUNE were acquired bilaterally and averaged at baseline/pre-injection (n=14), as well as 7 (n=14), 14 (n=14), 21 (n=6), and 28 (n=14) days post-injection. No baseline differences between groups were found. MUNE showed a significant change for time (p&lt;0.05), treatment (p&lt;0.001), and interaction time x treatment (p&lt;0.01) with ~40% reduction of MUNE in CTB-SAP rats. Average SMUP of CTB-SAP rats demonstrated a significant change with time (p&lt;0.05) and treatment (p&lt;0.01), but no significant interaction with ~50-60% increase in SMUP amplitude. CMAP showed no significant change. Our results show a significant ~40% loss of MUs in CTB-SAP rats, similar to previous studies on morphological MN counts. In parallel with MU loss, MUs enlarged (increased SMUP), consistent with compensatory increases of MU size likely through MU collateral sprouting. In conclusion, our findings suggest that the use of diaphragm MU electrophysiological measures can provide insights into the onset and progression of CTB-SAP-induced pathology concerning the loss of phrenic MU integrity. Hence, these biomarkers can be used to investigate mechanisms of phrenic motor neuron degeneration and compensation, and to expedite the translation of experimental findings to clinical testing. Supported by a Spinal Cord Injury and Disease Research grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

TNF-a Receptor 1 Activity Is Differentially Required for Phrenic Long-term Facilitation (pLTF) Over the Course of Motor Neuron Death in Adult Rats

Intrapleural injection of cholera toxin B fragment conjugated to saporin (CTB-SAP) selectively kills respiratory motor neurons, and mimics aspects of neuromuscular disorders and neurodegenerative diseases including phrenic motor neuron death, decreased phrenic motor output, and increased microglial cell number. Over the course of motor neuron loss, enhanced A2A receptor-dependent phrenic plasticity is observed early (7d), and then constrained 5-HT receptor-dependent phrenic plasticity is observed later (28d). In addition, COX-1/2-induced inflammation differentially impacts breathing and phrenic plasticity in CTB-SAP rats, but the underlying mechanism by which COX-1/2-induced inflammation impacts breathing and plasticity over the course of motor neuron death has not been studied. We observe that increased cervical neuroinflammatory gene expression ( e.g., tumor necrosis factor-a; TNF-a) is reduced back to control levels in the presence of ketoprofen in CTB-SAP rats, and it is known that TNF-a is involved in phrenic plasticity in naïve rats. Thus, we hypothesized that acute TNF-a receptor inhibition attenuates phrenic plasticity at 7d and enhances it at 28d TNF-a following CTB-SAP-induced neuropathology. Using anesthetized, paralyzed and ventilated CTB-SAP-treated adult Sprague Dawley rats, we studied acute intermittent hypoxia (AIH; 3, 5 min bouts of 10.5% O2) induced pLTF following acute intrathecal C4 delivery of a TNF-a receptor 1 inhibitor (soluble TNFR1; sTNFR1; 0.13 ug/ul) or vehicle (aCSF) to rats that received bilateral, intrapleural injections of: 1) CTB-SAP (25ug), or 2) un-conjugated CTB and SAP (control) in rats treated 7d or 28d prior. Surprisingly, preliminary results indicate that acute sTNFR1 delivery does not affect pLTF in 7d CTB-SAP-treated rats (n=5; i.e., pLTF still enhanced) but it enhanced pLTF in 28d CTB-SAP-treated rats (n=6; p&lt;0.05) vs. controls (n=6 at 7d; n=7 at 28d) and vs. vehicle treated rats (controls n=6 for 7d and n=9 for 28d; CTB-SAP, n=4 for 7d and 28d each). These preliminary observations suggest that TNF-a does not contribute to pLTF in 7d CTB-SAP-treated rats, whereas it may undermine pLTF in 28d CTB-SAP-treated rats. Studies are underway to assess the cellular source of TNF-a and the impact of chronic sTNFR1 delivery on pLTF, diaphragm activity, and breathing. Since most patients with neuromuscular disorders or neurodegenerative disease develop respiratory insuffciency and ultimately become ventilator dependent, our long-range goal is to develop new strategies to enhance the functional capacity of spared motor neurons and reduce ventilatory compromise in motor neuron loss pathology. These novel strategies, if successful, will identify new therapeutic targets for future, translational studies to enhance breathing in patients with neuromuscular disorders. Supported by a Spinal Cord Injury and Disease Research grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Back Stimulation with Gaussian Frequency Biphasic Burst Stimulation for Swallowing Motor Activation

Aspiration of food containing bacteria or saliva into the trachea, leading to bacterial lung infection, is termed aspiration pneumonia. In the United States, aspiration pneumonia results in over 57,000 deaths annually, constituting 2.3% of the total mortality. Similarly, according to data from 2021 in Japan, more than 49,000 individuals succumbed to aspiration pneumonia, accounting for approximately 3.4% of the total mortality, making it the sixth leading cause of death in Japan. Notably, the risk of mortality due to aspiration pneumonia can be mitigated through early detection and prevention of swallowing disorders. Consequently, this research focuses on rehabilitation strategies for swallowing disorders. Swallowing is a coordinated motor function, orchestrated by a program involving multiple muscles under the directives of the Swallow Central Pattern Generator (CPG) located in the medulla. Thus, activation of the Swallowing CPG is pivotal for effective swallowing rehabilitation. To this end, we propose a novel method to activate the Swallow CPG by electrical stimulating of the back. The back has been recognized as a site that activates the expiratory phase of respiration, where the swallow reflex is often triggered. Moreover, given the adjacency of the Swallowing CPG and the Respiratory CPG, we postulate that stimulating the back to activate the expiratory phase can lead to enhanced activation of swallowing movements. Methods: Surface electrodes were placed on the back (T9~T10) and neck of adult rats. Initially, burst stimuli of two polarities were randomly generated at frequencies of either 30 Hz or 300 Hz in accordance with a Gaussian distribution at one of the two sites. The electric stimuli were applied for 120 seconds, three times at each location. To evaluate the impact of stimulus frequency and location on swallowing movements, we compared four groups (n=4 in each group). Following stimulation at one site, identical waveforms of stimulation were administered to both the back and neck for 120 seconds, three times. Swallowing was induced by water injection into the mouth after each stimulation. Electromyography (EMG) of three swallow-related muscles (mylohyoid, thyroarytenoid, and thyropharyngeus) was recorded and their amplitudes compared, both before stimulation (control) and after six consecutive stimulations. Results: It was observed that stimulation of both the back and neck resulted in larger maximum muscle potentials in all measured cases. Furthermore, the lower frequency of 30 Hz yielded larger muscle potentials than 300 Hz. Statistical analysis revealed that back stimulation led to early activation of the thyropharyngeus muscle compared to neck stimulation. Conclusion: The discovery that burst electrical stimulation with Gaussian frequency applied to the back activates swallow muscle groups suggests a potential novel swallow therapy option. This work was supported by NIH grants HL 111215, HL 103415 and OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, the Commonwealth of Kentucky Challenge for Excellence, and Grant-in-Aid for JSPS Fellows Number JP23KJ0966. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Balloon compression-induced spinal cord injury in canines: a large animal model for spinal cord injury research.

Spinal cord injury (SCI) is a life-altering condition that severely impacts an individual's functional capabilities and has significant implications for both the individual and society. Large animal models are crucial for understanding the pathology and biomechanics of SCI. Dogs (Canis lupus familiaris) are promising models for SCI research due to their anatomical and histopathological similarities to humans. Balloon compression is an established method for inducing controlled SCI in canines. In this study, we optimized a balloon compression procedure for inducing SCI in dogs, aiming to develop a reliable model for future in vivo studies. Our methodology successfully induced total motoric loss in canines, observed for seven days, a critical period for therapeutic interventions. Histopathological examinations using Luxol fast blue (LFB) staining revealed total demyelination in intralesional samples, confirming the structural damage caused by balloon compression. We concluded that a balloon compression model at the T10-T11 vertebral level, with an inflated balloon volume of 1.0 ml, induced SCI while minimizing the risk of balloon rupture. Longer duration of compression ensures total paralysis in this model, providing a platform for testing therapeutic interventions during the acute phase of SCI. The canine model generated consistent data and facilitated straightforward observational findings.

The role of Patient and public involvement (PPI) in pre-clinical spinal cord research: An interview study.

Patient and public involvement in research (PPI) has many benefits including increasing relevance and impact. While using PPI in clinical research is now an established practice, the involvement of patients and the public in pre-clinical research, which takes place in a laboratory setting, has been less frequently described and presents specific challenges. This study aimed to explore the perspectives of seriously injured rugby players' who live with a spinal cord injury on PPI in pre-clinical research. Semi-structured interviews were conducted via telephone with 11 seriously injured rugby players living with spinal cord injury on the island of Ireland. A purposive sampling approach was used to identify participants. Selected individuals were invited to take part via gatekeeper in a charitable organisation that supports seriously injured rugby players. Interviews were transcribed verbatim and analysed thematically. Six themes were identified during analysis: 'appreciating potential benefits of PPI despite limited knowledge', 'the informed perspectives of people living with spinal cord injury can improve pre-clinical research relevance', 'making pre-clinical research more accessible reduces the potential for misunderstandings to occur', 'barriers to involvement include disinterest, accessibility issues, and fear of losing hope if results are negative', 'personal contact and dialogue helps people feel valued in pre-clinical research, and 'PPI can facilitate effective dissemination of pre-clinical research as desired by people living with spinal cord injury.' People affected by spinal cord injury in this study desire further involvement in pre-clinical spinal cord injury research through dialogue and contact with researchers. Sharing experiences of spinal cord injury can form the basis of PPI for pre-clinical spinal cord injury research.

Development and psychometric properties of appraisals of post traumatic spinal cord injury health scale in Iran.

Development and psychometrics study OBJECTIVE: To evaluate the reliability and validity of a new version of Appraisals of Post-Traumatic Spinal Cord Injury Health Scale (APTSCIHS) in the Persian language for persons with spinal cord injury (SCI). The persons were selected from National Spinal Cord Injury Registry of Iran (NSCIR-IR) and Brain and Spinal Cord Injury Research center (BASIR). This was a mixed sequential exploratory study that performed in two phases. In the qualitative phase, a systematic scoping review and 12 interviews with the participants were done. Finally, items were generated. In the quantitative phase, face, content, construct and convergent validity were assessed to evaluate validity. To evaluate construct validity, a cross-sectional study was conducted on 305 persons with TSCI along with internal consistency and stability assessments. All quantitative data analyses were conducted using SPSS 22 software. The content validity and reliability were indicated by Scale's Content Validity Ratio (S-CVR) = 0.73 and Scale's Content Validity Index (S-CVI) = 0.86, Cronbach's α = 0.9 and the Test re-test reliability using intra-class correlations were (ICC) = 0.97 to 0.98. Exploratory factor analysis determined eight factors which showed more than 52% of the variance. APTSCIHS had a significant and strong correlation with Appraisals of DisAbility Primary and Secondary Scale (ADAPSS) (r = 0.475, P < 0.001). Results showed the 36 items APTSCIHS tool had an acceptable validity and reliability in Iran, and it can help health care providers or even administrators improve the quality of the rehabilitation services and quality of life.

Global Research Trends on Gait Rehabilitation in Individuals With Spinal Cord Injury- A Bibliometric Analysis.

Bibliometric analysis. The study aims to comprehensively assess the literature related to gait rehabilitation for individuals with spinal cord injury (SCI) to identify significant contributors, and to explore the collaborations and emerging themes in the field. Original and review articles in English using relevant keywords were searched in the Clarivate Web of Science database. The data from the selected articles were imported into R software. Bibliometric indicators were assessed to determine author contributions, country affiliations, journal sources, and thematic trends. A total of 1313 relevant articles were identified. The USA, followed by Canada and Switzerland were the most prolific countries contributing to gait rehabilitation research in SCI. The most relevant journals were Spinal Cord, Archives of Physical Medicine and Rehabilitation, Journal of Spinal Cord Medicine, Journal of NeuroEngineering, and Journal of Neurotrauma. The highest contributions came from Northwestern University, the University of Miami, and the University of Alberta. The analysis revealed an increase in research interest in gait rehabilitation after 2000, with a focus on interdisciplinary approaches and emerging technologies like robotics, exoskeletons, and neuromodulation. The analysis demonstrates the importance of collaborative and interdisciplinary research in gait rehabilitation. The results indicate a shift in research focus from traditional methods to the integration of technology. The impact of publications from the USA and Europe is a notable finding. The study highlights the growth of articles related to technology-driven approaches and understanding neuroplasticity in gait rehabilitation.

Toward a person-centered ethics framework for autonomy in spinal cord injury research and rehabilitation.

In this paper, we explore how the concepts of autonomy and autonomous choice are understood in the context of spinal cord injury in the academic literature, both in reporting on research results and more broadly on outcomes and quality of life. We find inconsistent, framework-absent portrayals of autonomy as well as an absence of discourse that draws upon ethical constructs and theory. In response, we advance a person-centered framework for spinal cord injury research that combines both lived experience and a disability ethics approach to fill this gap.

Multi-session transcutaneous spinal cord stimulation prevents chloride homeostasis imbalance and the development of hyperreflexia after spinal cord injury in rat

Spasticity is a complex and multidimensional disorder that impacts nearly 75% of individuals with spinal cord injury (SCI) and currently lacks adequate treatment options. This sensorimotor condition is burdensome as hyperexcitability of reflex pathways result in exacerbated reflex responses, co-contractions of antagonistic muscles, and involuntary movements. Transcutaneous spinal cord stimulation (tSCS) has become a popular tool in the human SCI research field. The likeliness for this intervention to be successful as a noninvasive anti-spastic therapy after SCI is suggested by a mild and transitory improvement in spastic symptoms following a single stimulation session, but it remains to be determined if repeated tSCS over the course of weeks can produce more profound effects. Despite its popularity, the neuroplasticity induced by tSCS also remains widely unexplored, particularly due to the lack of suitable animal models to investigate this intervention. Thus, the basis of this work was to use tSCS over multiple sessions (multi-session tSCS) in a rat model to target spasticity after SCI and identify the long-term physiological improvements and anatomical neuroplasticity occurring in the spinal cord. Here, we show that multi-session tSCS in rats with an incomplete (severe T9 contusion) SCI (1) decreases hyperreflexia, (2) increases the low frequency-dependent modulation of the H-reflex, (3) prevents potassium-chloride cotransporter isoform 2 (KCC2) membrane downregulation in lumbar motoneurons, and (4) generally augments motor output, i.e., EMG amplitude in response to single pulses of tSCS, particularly in extensor muscles. Together, this work displays that multi-session tSCS can target and diminish spasticity after SCI as an alternative to pharmacological interventions and begins to highlight the underlying neuroplasticity contributing to its success in improving functional recovery.